NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction.

The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.

Analysis of maternal genetic structure of mitochondrial DNA control region from Tai-Kadai-speaking Buyei population in southwestern China.

BACKGROUND: Even though the Buyei are a recognised ethnic group in southwestern China, there hasn't been much work done on forensic population genetics, notably using mitochondrial DNA. The sequences and haplogroups of mitochondrial DNA control regions of the Buyei peoples were studied to provide support for the establishment of a reference database for forensic DNA analysis in East Asia. METHODS AND RESULTS: The mitochondrial DNA control region sequences of 200 Buyei individuals in Guizhou were investigated. The haplotype frequencies and haplogroup distribution of the Buyei nationality in Guizhou were calculated. At the same time, the paired Fst values of the study population and other populations around the world were computed, to explore their genetic polymorphism and population relationship. A total of 179 haplotypes were detected in the Buyei population, with frequencies of 0.005-0.015. All haplotypes were assigned to 89 different haplogroups. The haplotype diversity and random matching probability were 0.999283 and 0.0063, respectively. The paired Fst genetic distances and correlation p-values among the 54 populations revealed that the Guizhou Buyei was most closely related to the Henan Han and the Guizhou Miao, and closer to the Hazara population in Pakistan and the Chiang Mai population. CONCLUSIONS: The study of mitochondrial DNA based on the maternal genetic structure of the Buyei nationality in Guizhou will benefit the establishment of an East Asian forensic DNA reference database and provide a reference for anthropological research in the future.

Developmental and validation of a novel small and high-efficient panel of microhaplotypes for forensic genetics by the next generation sequencing.

BACKGROUND: In the domain of forensic science, the application of kinship identification and mixture deconvolution techniques are of critical importance, providing robust scientific evidence for the resolution of complex cases. Microhaplotypes, as the emerging class of genetic markers, have been widely studied in forensics due to their high polymorphisms and excellent stability. RESULTS AND DISCUSSION: In this research, a novel and high-efficient panel integrating 33 microhaplotype loci along with a sex-determining locus was developed by the next generation sequencing technology. In addition, we also assessed its forensic utility and delved into its capacity for kinship analysis and mixture deconvolution. The average effective number of alleles (Ae) of the 33 microhaplotype loci in the Guizhou Han population was 6.06, and the Ae values of 30 loci were greater than 5. The cumulative power of discrimination and cumulative power of exclusion values of the novel panel in the Guizhou Han population were 1-5.6 × 10- 43 and 1-1.6 × 10- 15, respectively. In the simulated kinship analysis, the panel could effectively distinguish between parent-child, full-sibling, half-sibling, grandfather-grandson, aunt-nephew and unrelated individuals, but uncertainty rates clearly increased when distinguishing between first cousins and unrelated individuals. For the mixtures, the novel panel had demonstrated excellent performance in estimating the number of contributors of mixtures with 1 to 5 contributors in combination with the machine learning methods. CONCLUSIONS: In summary, we have developed a small and high-efficient panel for forensic genetics, which could provide novel insights into forensic complex kinships testing and mixture deconvolution.

Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

Succession changes of microbial community for inferring the time since deposition of saliva.

Saliva is a common biological examination material at crime scenes and has high application value in forensic case investigations. It can reflect the suspect's time of crime at the scene and provide evidence of the suspect's criminal facts. Even though many researchers have proposed their experimental protocols for estimating the time since deposition (TsD) of saliva, there is still a relative lack of research on the use of microorganisms to estimate TsD. In the current study, the succession change of microbial community in saliva with different TsD values was explored to discern the microbial markers related to TsD of saliva. We gathered saliva samples from six unrelated healthy Han individuals living in Guizhou, China and exposed these samples to indoor conditions at six time points (0, 1, 3, 7, 15, and 28 days). Temporal changes of microbial compositions in these samples were investigated by 16S rRNA sequencing (V3-V4 regions). By assessing temporal variation patterns of microbial abundance at the genus level, four bacteria (Brucella, Prevotella, Pseudomonas, and Fusobacterium) were observed to show good time dependence in these samples. In addition, the hierarchical clustering and principal co-ordinates analysis results revealed that these saliva samples could be classified into t-short (≤7 days) and t-long (>7 days) groups. In the end, the random forest model was developed to predict the TsD of these samples. For the model, the root mean square error, R2, and mean absolute error between predicted and actual TsD values were 1.5213, 0.9851, and 1.1969, respectively. To sum up, we identified TsD-related microbial markers in saliva samples, which could be viewed as valuable markers for inferring the TsD of saliva.

Associations between prenatal exposure to per- and polyfluoroalkyl substances and plasma immune molecules in three-year-old children in China.

BACKGROUND: Many studies have reported that prenatal exposure to Per- and Polyfluoroalkyl Substances (PFASs) can disrupt immune function. However, little is known about the effects of PFASs on immune molecules. The study analyzed the association between prenatal exposure to mixed and single PFASs and plasma immune molecules in three-year-old children. METHODS: Ten PFASs were measured in umbilical cord serum, while peripheral blood samples were collected at age three to measure immune molecules. Associations between exposure to individual and combined PFASs and immune molecules were analyzed using Generalized Linear Models and Weighted Quantile Sum (WQS) regression. RESULTS: (1) Interleukin-4 (IL-4) increased by 23.85% (95% CI:2.99,48.94) with each doubling of Perfluorooctanoic Acid (PFOA), and Interleukin-6 (IL-6) increased by 39.07% (95%CI:4.06,85.86) with Perfluorotridecanoic Acid (PFTrDA). Elevated PFOA and Perfluorononanoic Acid (PFNA) were correlated with increases of 34.06% (95% CI: 6.41, 70.28) and 24.41% (95% CI: 0.99, 53.27) in Eotaxin-3, respectively. Additionally, the doubling of Perfluorohexane Sulfonic Acid (PFHxS) was associated with a 9.51% decrease in Periostin (95% CI: -17.84, -0.33). (2) The WQS analysis revealed that mixed PFASs were associated with increased IL-6 (ß = 0.37, 95%CI:0.04,0.69), mainly driven by PFTrDA, PFNA, and 8:2 Chlorinated Perfluoroethyl Sulfonamide (8:2 Cl-PFESA). Moreover, mixed PFASs were linked to an increase in Eotaxin-3 (ß = 0.32, 95% CI: 0.09,0.55), primarily influenced by PFOA, PFTrDA, and Perfluorododecanoic Acid (PFDoDA). CONCLUSIONS: Prenatal PFASs exposure significantly alters the levels of immune molecules in three-year-old children, highlighting the importance of understanding environmental impacts on early immune development.

Effects of different VV ECMO blood flow rates on lung perfusion assessment by hypertonic saline bolus-based electrical impedance tomography.

OBJECTIVE: Our study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO. METHODS: In this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared. RESULTS: Fifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93-42.16)% to 41.29 (35.32-43.75)%, p = 0.003, and 48.86 (45.53-58.96)% to 54.12 (45.07-61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42-9.78)% to 6.08 (5.27-9.34)%, p = 0.049, and 51.14 (41.04-54.47)% to 45.88 (38.84-54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt. CONCLUSIONS: During VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.

Assessment of nonylphenol exposure based on global urinary concentration data and its risk analysis.

Nonylphenol (NP) has been recognized as a priority hazardous substance because of its estrogenic activity and ubiquity in the environment. Therefore, it is important to understand the daily intake of NP in humans and evaluate the potential health risks of NP. The median or average estimated daily intake (EDI) of NP was estimated based on urinary NP or alkyl-chain-oxidized NP metabolites concentration data from published epidemiological studies. In brief, we acquired 34 peer-reviewed publications, which contained 14235 samples from twelve countries or regions. The global average estimated daily intake of NP was 1.003 µg/(kg bw·day), which was lower than the tolerable daily intake recommended by the Danish Veterinary and Food Authority [5 µg/(kg bw·day)]. Korea had the highest exposure level [3.471 µg/(kg bw·day)] among different countries or regions. Compared with the adult [0.743 µg/(kg bw·day)] and pregnant women [0.806 µg/(kg bw·day)] groups, the children group had the highest estimated daily intake of NP at 2.368 µg/(kg bw·day). Besides, the global NP risk hazard quotient was 0.201, and the risk hazard quotients of all countries or regions were less than 1. However, the global HQ value of the 95th quantile population was 2.299, which was much higher than 1, the potential health risk cannot be ignored and needs to be confirmed by more research. To our knowledge, this is the first study to assess the overall NP exposure levels based on published biomonitoring data, and has important implications for assessing the potential effects of NP exposure on human health. In addition, OH-NP is a robust and sensitive novel biomarker for NP, there are fewer studies on the application of this biomarker, and more studies are needed in the future for quantitative exposure and risk assessment of NP.

Effect of Thyroid-Stimulating Hormone Suppression Therapy on Cardiac Structure and Function in Patients With Differentiated Thyroid Cancer After Thyroidectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: We aimed to evaluate the effects of thyroid-stimulating hormone (TSH) suppression therapy on cardiac structure and function in patients with differentiated thyroid cancer (DTC) following thyroidectomy. METHODS: Two investigators independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant studies published from inception to January 6, 2023, without any restrictions on language. Standard mean differences and 95% confidence intervals were calculated using fixed or random effects models. Thirteen clinical outcomes were analyzed, mainly evaluating cardiac morphology, systolic function, and diastolic function. RESULTS: Thirteen studies were included in the quantitative analysis. Compared to healthy controls, left ventricular mass index, left ventricular posterior wall thickness, interventricular septal thickness, and isovolumic relaxation time values increased; the ratio of E-wave velocity to A-wave velocity and E-wave velocity values decreased. The left ventricular ejection fraction and cardiac output did not change in patients with DTC who underwent long-term TSH suppression therapy. Interventricular septal thickness values were significantly correlated with the duration of TSH suppression therapy. CONCLUSION: Long-term TSH suppression therapy leads to cardiac hypertrophy and impaired cardiac diastolic function in patients with DTC. These changes may be related to the duration of TSH suppression therapy. Large prospective studies with long follow-up periods are needed to validate these findings.

Varieties of P fractions in biochar-amended reconstructed soils as impacted by freeze-thaw interference.

With low cost and stable chemical properties, biochar has great potential in environmental pollution control and improving soil quality. Reusing tailings slag to reconstruct soil ecosystems and applying amendments such as biochar to enhance soil quality are significant for restoring waste mine lands. Phosphorus (P) as the restrictive nutrition element for plant growth is easily affected by freeze-thaw cycles (FTCs). However, effective information about FTCs on P dynamics in biochar-amended reconstructed soil is scanty. To further understand the effect of FTCs on P in reclaimed mine soils, three reconstructed soils composed of equal brown soil and tailings slag with the respective application of no amendment, 5% biochar and 5% powder both derived from Gleditsia japonica shells (GS), were prepared to evaluate P fraction changes after FTCs. The results indicated that GS biochar increased soil pH, total organic matter (TOM), and moisture content (MC). GS biomass had a similar impact on TOM and MC but decreased soil pH. The two agricultural amendments increased active P and microbial biomass P (MBP) by 46.13%-101.63% and 162.8%-185.7%, which might be largely contributed by soil organic matter and moisture. FTC numbers (0, 3, 6, 10, 15) significantly decreased MBP contents and slightly converted non-labile P into labile fractions while FTC temperature (-20∼5 °C and -10∼5 °C) hardly influenced soil P behavior. In addition, GS conditioners simultaneously enhanced available P content and P fixation potential by soil under FTCs.

Preparing a novel baicalin-loaded microemulsion-based gel for transdermal delivery and testing its anti-gout effect.

We previously demonstrated that baicalin had efficacy against gouty arthritis (GA) by oral administration. In this paper, a novel baicalin-loaded microemulsion-based gel (B-MEG) was prepared and assessed for the transdermal delivery of baicalin against GA. The preparation method and transdermal capability of B-MEG was screened and optimized using the central composite design, Franz diffusion cell experiments, and the split-split plot design. Skin irritation tests were performed in guinea pigs. The anti-gout effects were evaluated using mice. The optimized B-MEG comprised of 50 % pH 7.4 phosphate buffered saline, 4.48 % ethyl oleate, 31.64 % tween 80, 13.88 % glycerin, 2 % borneol, 0.5 % clove oil and 0.5 % xanthan gum, with a baicalin content of (10.42 ± 0.08) mg/g and particle size of (15.71 ± 0.41) nm. After 12 h, the cumulative amount of baicalin permeated from B-MEG was (672.14 ± 44.11) µg·cm-2. No significant skin irritation was observed following B-MEG application. Compared to the model group, B-MEG groups significantly decreased the rate of auricular swelling (P < 0.01) and number of twists observed in mice (P < 0.01); and also reduced the rate of paw swelling (P < 0.01) and inflammatory cell infiltration in a mouse model of GA. In conclusion, B-MEG represents a promising transdermal carrier for baicalin delivery and can be used as a potential therapy for GA.

A chromosome-level genome of Syringa oblata provides new insights into chromosome formation in Oleaceae and evolutionary history of lilacs.

Lilacs (Syringa L.), a group of well-known ornamental and aromatic woody plants, have long been used for gardening, essential oils and medicine purposes in East Asia and Europe. The lack of knowledge about the complete genome of Syringa not only hampers effort to better understand its evolutionary history, but also prevents genome-based functional gene mining that can help in the variety improvement and medicine development. Here, a chromosome-level genome of Syringa oblata is presented, which has a size of 1.12 Gb including 53 944 protein coding genes. Synteny analysis revealed that a recent duplication event and parallel evolution of two subgenomes formed the current karyotype. Evolutionary analysis, transcriptomics and metabolic profiling showed that segment and tandem duplications contributed to scent formation in the woody aromatic species. Moreover, phylogenetic analysis indicated that S. oblata shared a common ancestor with Osmanthus fragrans and Olea europaea approximately 27.61 million years ago (Mya). Biogeographic reconstruction based on a resequenced data set of 26 species suggested that Syringa originated in the northern part of East Asia during the Miocene (approximately 14.73 Mya) and that the five Syringa groups initially formed before the Late Miocene (approximately 9.97 Mya). Furthermore, multidirectional dispersals accompanied by gene introgression among Syringa species from Northern China during the Miocene were detected by biogeographic reconstruction. Taken together, the results showed that complex gene introgression, which occurred during speciation history, greatly contributed to Syringa diversity.

Genomic formation of Tibeto-Burman speaking populations in Guizhou, Southwest China.

Sino-Tibetan is the most prominent language family in East Asia. Previous genetic studies mainly focused on the Tibetan and Han Chinese populations. However, due to the sparse sampling, the genetic structure and admixture history of Tibeto-Burman-speaking populations in the low-altitude region of Southwest China still need to be clarified. We collected DNA from 157 individuals from four Tibeto-Burman-speaking groups from the Guizhou province in Southwest China. We genotyped the samples at about 700,000 genome-wide single nucleotide polymorphisms. Our results indicate that the genetic variation of the four Tibeto-Burman-speaking groups in Guizhou is at the intermediate position in the modern Tibetan-Tai-Kadai/Austronesian genetic cline. This suggests that the formation of Tibetan-Burman groups involved a large-scale gene flow from lowland southern Chinese. The southern ancestry could be further modelled as deriving from Vietnam's Late Neolithic-related inland Southeast Asia agricultural populations and Taiwan's Iron Age-related coastal rice-farming populations. Compared to the Tibeto-Burman speakers in the Tibetan-Yi Corridor reported previously, the Tibeto-Burman groups in the Guizhou region received additional gene flow from the southeast coastal area of China. We show a difference between the genetic profiles of the Tibeto-Burman speakers of the Tibetan-Yi Corridor and the Guizhou province. Vast mountain ranges and rivers in Southwest China may have decelerated the westward expansion of the southeast coastal East Asians. Our results demonstrate the complex genetic profile in the Guizhou region in Southwest China and support the multiple waves of human migration in the southern area of East Asia.

Innate Immune Evasion of Porcine Epidemic Diarrhea Virus through Degradation of the FBXW7 Protein via the Ubiquitin-Proteasome Pathway.

Porcine epidemic diarrhea virus (PEDV) causes a porcine disease associated with swine epidemic diarrhea. Different antagonistic strategies have been identified, and the mechanism by which PEDV infection impairs the production of interferon (IFN) and delays the activation of the IFN response to escape host innate immunity has been determined, but the pathogenic mechanisms of PEDV infection remain enigmatic. Our preliminary results revealed that endogenous F-box and WD repeat domain-containing 7 (FBXW7) protein, the substrate recognition component of the SCF-type E3 ubiquitin ligase, is downregulated in PEDV-infected Vero E6 cells, according to the results from an isobaric tags for relative and absolute quantification (iTRAQ) analysis. Overexpression of FBXW7 in target cells makes them more resistant to PEDV infection, whereas ablation of FBXW7 expression by small interfering RNA (siRNA) significantly promotes PEDV infection. In addition, FBXW7 was verified as an innate antiviral factor capable of enhancing the expression of RIG-I and TBK1, and it was found to induce interferon-stimulated genes (ISGs), which led to an elevated antiviral state of the host cells. Moreover, we revealed that PEDV nonstructural protein 2 (nsp2) interacts with FBXW7 and targets FBXW7 for degradation through the K48-linked ubiquitin-proteasome pathway. Consistent with the results proven in vitro, FBXW7 reduction was also confirmed in different intestinal tissues from PEDV-infected specific-pathogen-free (SPF) pigs. Taken together, the data indicated that PEDV has evolved with a distinct antagonistic strategy to circumvent the host antiviral response by targeting the ubiquitin-proteasome-mediated degradation of FBXW7. Our findings provide novel insights into PEDV infection and pathogenesis. IMPORTANCE To counteract the host antiviral defenses, most viruses, including coronaviruses, have evolved with diverse strategies to dampen host IFN-mediated antiviral response, by interfering with or evading specific host regulators at multiple steps of this response. In this study, a novel antagonistic strategy was revealed showing that PEDV infection could circumvent the host innate response by targeted degradation of endogenous FBXW7 in target cells, a process that was verified to be a positive modulator for the host innate immune system. Degradation of FBXW7 hampers host innate antiviral activation and facilitates PEDV replication. Our findings reveal a new mechanism exploited by PEDV to suppress the host antiviral response.

Systematic selection of ancestry informative SNPs for differentiating Han, Japanese, Dai, and Kinh populations.

Biogeographical origin inferences of different populations can provide valuable clues in the forensic investigation by narrowing down the detection scope. However, much research mainly focuses on forensic ancestral origin analyses of major continental populations, which may provide limited information in forensic practice. To improve the ancestral resolution of East Asian populations, we systematically selected ancestry informative single-nucleotide polymorphisms (AISNPs) for differentiating Han, Dai, Japanese, and Kinh populations. In addition, we evaluated the performance of the selected AISNPs to differentiate these populations via multiple methods. Totally 116 AISNPs were selected from the genome-wide data to infer the population origins of these four populations. Results of principle component analysis and population genetic structure of these populations indicated that the selected 116 AISNPs could achieve ancestral resolution of most individuals. Furthermore, the machine learning model built by 116 AISNPs unveiled that most individuals from these four populations could be assigned to correct population origins. To sum up, the selected 116 SNPs could be available for ancestral origin predictions of Han, Dai, Japanese, and Kinh populations, which could provide valuable information for forensic research and genome-wide association study in East Asian populations to some extent.

Effects of airway pressure release ventilation on lung physiology assessed by electrical impedance tomography in patients with early moderate-to-severe ARDS.

OBJECTIVE: The aim of this study was to investigate the physiological impact of airway pressure release ventilation (APRV) on patients with early moderate-to-severe acute respiratory distress syndrome (ARDS) by electrical impedance tomography (EIT). METHODS: In this single-center prospective physiological study, adult patients with early moderate-to-severe ARDS mechanically ventilated with APRV were assessed by EIT shortly after APRV (T0), and 6 h (T1), 12 h (T2), and 24 h (T3) after APRV initiation. Regional ventilation and perfusion distribution, dead space (%), shunt (%), and ventilation/perfusion matching (%) based on EIT measurement at different time points were compared. Additionally, clinical variables related to respiratory and hemodynamic condition were analyzed. RESULTS: Twelve patients were included in the study. After APRV, lung ventilation and perfusion were significantly redistributed to dorsal region. One indicator of ventilation distribution heterogeneity is the global inhomogeneity index, which decreased gradually [0.61 (0.55-0.62) to 0.50 (0.42-0.53), p < 0.001]. The other is the center of ventilation, which gradually shifted towards the dorsal region (43.31 ± 5.07 to 46.84 ± 4.96%, p = 0.048). The dorsal ventilation/perfusion matching increased significantly from T0 to T3 (25.72 ± 9.01 to 29.80 ± 7.19%, p = 0.007). Better dorsal ventilation (%) was significantly correlated with higher PaO2/FiO2 (r = 0.624, p = 0.001) and lower PaCO2 (r = -0.408, p = 0.048). CONCLUSIONS: APRV optimizes the distribution of ventilation and perfusion, reducing lung heterogeneity, which potentially reduces the risk of ventilator-induced lung injury.

Association of arsenic exposure and clinical hematological changes during pregnancy: Findings from a prospective Wuhan birth cohort study.

BACKGROUND: Animal studies have reported arsenic-induced disturbed erythropoiesis parameters. However, the effects of exposure to arsenic on hematological parameters among pregnant women are unclear. OBJECTIVES: We aimed to evaluate trimester-specific associations between arsenic metabolites and erythropoietic parameters measured repeatedly during pregnancy. METHODS: A total of 1945 pregnant women from a birth cohort study were included. We detected arsenic species in urine sampled at each trimester and extracted erythropoietic parameters in different trimesters from the medical records. We used linear regressions with generalized estimating equations (GEEs) to examine the relationship between arsenic metabolites concentrations at different trimesters and erythropoietic parameters. We utilized GEEs to calculate the odds ratio (OR) for anemia during pregnancy. RESULTS: Adjusted trimester-specific analysis showed that higher monomethylated arsenic (MMA) and %MMA were related to remarkably reduced hemoglobin (Hb) and mean corpuscular hemoglobin (MCH). Additionally, elevated urinary MMA concentration and %MMA in the early trimester were associated with an increased risk of microcytic anemias in the late trimester. CONCLUSIONS: Our study demonstrated a significant inverse relationship between gestational arsenic exposure and Hb and MCH. Notably, higher MMA and lower methylation capacity to metabolize inorganic arsenic (iAs) in early pregnancy might increase the likelihood of microcytic anemia among pregnant women in late pregnancy.

Effect of blood pressure variability on hypertensive retinopathy.

PURPOSE: This study intends to investigate the correlation between blood pressure variability (BPV) levels and the use of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal microvasculature in hypertensive patients. METHODS: All individuals in the study had 24-hour ambulatory blood pressure monitoring and bilateral OCT and OCTA exams, and only data from the right eye were analyzed statistically. RESULTS: The study included 170 individuals, with 60 in the control group. The experimental group was separated into two groups based on the average real variability (ARV) median, with 55 in the low ARV group and 55 in the high ARV group. The mean thicknesses of the Retinal Nerve Fiber Layer (RNFL), internal limiting membrane-retinal pigment epithelial cell layer (ILM-RPE), vessel density (VD), and perfusion density (PD) in the high-ARV group were substantially lower in the low-ARV and control groups (p＜0.05). Multiple linear regression analysis revealed that disease duration, age, and 24 h diastolic standard deviation all affected RNFL mean thickness (p＜0.05). VD and PD were influenced by disease duration, systolic-ARV, daytime systolic blood pressure, intraocular pressure(IOP), and best-corrected visual acuity (BCVA) (p＜0.05). And the change in VD was connected to best-corrected visual acuity. CONCLUSION: Hypertensive retinopathy is related to BPV. In clinical practice, we can assess the degree of BPV and retinopathy in hypertensive patients to track the progression of hypertension-mediated organ damage (HMOD). Correction of BPV may help treat or postpone the progression of HOMD.

Associations of arsenic exposure with blood pressure and platelet indices in pregnant women: A cross-sectional study in Wuhan, China.

BACKGROUND: Environmental inorganic arsenic (iAs) exposure is potentially related to abnormal blood pressure (BP) changes and abnormal platelet activation. However, limited epidemiological studies have explored the impacts of iAs exposure on platelet change mediated by BP, especially for pregnant women. OBJECTIVES: Our purpose was to investigate the associations of arsenic exposure with blood pressure and platelet indices among pregnant women. METHODS: The present study population included 765 pregnant women drawn from a prospective birth cohort study in Wuhan, China, recruited between October 2013 and April 2016. Urine sampled in the second trimester were used to assess arsenic species concentrations. The relative distribution of urinary arsenic species was used to measure human methylation capacity. BP parameters and platelet indices originated from the medical record. We applied multivariable linear regression models to explore the cross-sectional relationships between urinary arsenic metabolites, BP parameters, and platelet indices. We utilized mediation analysis to investigate the impacts of arsenic exposure on platelet indices through BP as mediator variables. RESULTS: We observed significant positive correlations between iAs and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Pregnant women with higher methylation capacity to metabolize iAs characterized by higher secondary methylation index (SMI) and total methylation index (TMI) had a more significant reduction in SBP, DBP, and MAP. Pregnant women with higher DBP and MAP had higher platelet counts (PLC). A decreased PLC was found in subjects wither higher SMI. Additionally, SMI was negatively linked to PLC mediated through MAP. CONCLUSIONS: Obtained results suggested that higher methylation capacity to metabolize iAs might contribute to decreased PLC among pregnant women, and MAP might mediate the influence of SMI on PLC.

Forensic efficiency evaluation of a novel multiplex panel of InDels and STRs in the Guizhou Han population and its phylogenetic relationships with other reference populations.

BACKGROUND: Insertion/deletion polymorphism (InDel), as the third genetic marker, has been given a lot of attention by forensic geneticists since it has the advantages of extensive distributions in the human genome, small amplicon, and low mutation rate. However, the extant InDel panels were only viewed as supplemental tools for kinship analyses. In addition, these panels were not conductive to mixture deconvolution because InDels in these panels mainly displayed two alleles. AIMS: The purpose of this study is to investigate genetic distributions of a novel panel of InDels and STRs in the Guizhou Han population; assess the forensic application value of the panel; and conduct population genetic analyses of the Guizhou Han and other reference populations based on the overlapping loci. SUBJECTS AND METHODS: The bloodstain samples of 209 Guizhou Han were gathered and genotyped by the novel panel. Allelic frequencies and forensic parameters of two miniSTRs and 59 InDels in the panel were estimated. In addition, we assessed phylogenetic relationships among the Guizhou Han and other reference populations by principal component analysis, DA genetic distance, and neighbor-joining tree. RESULTS: A total of 139 alleles of 61 loci could be observed in the Guizhou Han population. Polymorphic information content values of 59 InDels were greater than 0.3 in the Guizhou Han population. The cumulative power of discrimination and probability of exclusion of two miniSTRs and 59 InDels in the Guizhou Han population were 0.999999999999999999999999997984 and 0.9999986, respectively. Principal component analysis of 14 populations showed that the Guizhou Han population located closer to Hunan Han and Southern Han Chinese (CHS) populations. Similar results were also discerned from DA genetic distances and the neighbor-joining tree. CONCLUSION: To sum up, the novel panel could be employed for forensic personal identification and paternity testing in the Guizhou Han population as a promising independent tool. Besides, the principal component analysis and phylogenetic tree of the Guizhou Han and other compared populations revealed that the Guizhou Han population possesses close genetic affinities with Hunan Han, CHS, and Han Chinese in Beijing (CHB) populations.